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Determination of HLA‐A*02 antigen status in Hodgkin's disease and analysis of an HLA‐A*02‐restricted epitope of the Epstein‐Barr virus LMP‐2 protein
Author(s) -
Bryden Helen,
MacKenzie Jane,
Andrew Linda,
Alexander Freda E.,
Angus Brian,
Krajewski Andrew S.,
Armstrong Alison A.,
Gray Diane,
Cartwright Ray A.,
Kane Eleanor,
Wright Denis H.,
Taylor Penny,
Jarrett Ruth F.
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970807)72:4<614::aid-ijc11>3.0.co;2-b
Subject(s) - epitope , human leukocyte antigen , biology , antigen , virology , virus , epstein–barr virus , cytotoxic t cell , hla a , immunology , microbiology and biotechnology , genetics , in vitro
There is good evidence for an association between Epstein‐Barr virus (EBV) and Hodgkin's disease (HD). In approximately one‐third of cases, the EBV genome is detectable in Reed‐Sternberg (RS) cells and there is expression of the viral nuclear antigen EBNA‐1 and the latent membrane protein LMP‐1. Expression of LMP‐2 has been demonstrated at the mRNA level, and it is presumed that the protein is expressed alongside LMP‐1. The LMP‐2 protein is known to contain an epitope presented to cytotoxic T‐cells which is restricted through the HLA class I antigen A*0201 in healthy seropositive individuals. Since most HLA‐A*02‐positive Caucasians are HLA‐A*0201‐positive, it was hypothesized that HLA‐A*02‐positive individuals would be under‐represented among Caucasians with EBV‐associated HD. HLA‐A*02 status was determined, using flow cytometry and/or the polymerase chain reaction, for 276 individuals including 176 cases of HD. There was no significant difference between the frequency of HLA‐A*02 positivity in HD cases and controls, and between EBV‐associated and non‐associated cases of HD. The A*02 alleles of 14 cases of EBV‐associated HD were further subtyped using nested PCR; all except one case were found to be A*0201 ‐positive. We therefore investigated whether there was any evidence for mutation of the epitope representing amino acids 426–434 of LMP‐2a which is restricted through HLA‐A*0201. In 10/11 cases the nucleotide sequence encoding this epitope was identical to the published sequence; in the remaining case there was a mutation which would not be expected to alter the conformation of the epitope. Overall, our data suggest that other mechanisms of immune escape must be operative in EBV‐associated HD. Int. J. Cancer 72:614–618, 1997. © 1997 Wiley‐Liss, Inc.